You could always try to somehow get the genetic material to allow you to bring backbear-dogs. Some of those got over a thousand pounds. They were never domesticated, though, so would probably cause problems.
Not to debate us killing them and their habitat off, because we most certainly did, but even before that, Lions had a specific range.
Where the remaining megafauna was.
Which was ALL of africa, some of southern europe, some of southern asia, and east central india.
That’s pretty much the confines of his yard since 10,000ya
Mother nature stopped delivering the large grocery items outside this area, and the lion retreated back towards africa (or just flat out died in some places)
30 lions have a hard way to go when no one is delivering zebra and wildebeest, so they have to stay in the delivery area so to speak. The closing of the Quaternary grocery store saw to that.
So we get a new world where large pack cat gets confined niche to exist in, because it is the only place that can feed them, and small little pack wolf just exists everywhere, and most of those places do not support a 500 to 600 pound pack predator living in family groups of 15 to 30 animals.
It bears mentioning again, that the african/asiatic lion is very unique in having either adopted a very non feline trait of social pack behavior (even if they don’t quite have the social part down pat) or being the only feline to retain this living structure.
Then again, foxes, long departed from wolves kind of live more like cats in the social aspect.
Might make an interesting other discussion
Wolf and Cat already had their arms race.
Wolf topped out around 200 pounds, Cat topped out at around 1000 pounds.
Wolf has always been the little guy, nature did not see the need to equip him with the structure of a 500 to 1000 pound predator.
We bastardised the wolf quite a lot over the last 10,000 years, but we aren’t bright enough to, let’s say, tell a structure to change from flat to beamed design, when there is not even a precedent in the organisms past, that would be custom made genetics.
That’s why god created Walmarts and people who shop at Walmarts — to feed the 600 lb dogs.
They were not domesticated because they died off about 2 million years ago.
They also are not dogs, nor wolves, nor anything close enough, different family.
Wolf and fox are closer and even they can not interbreed.
“Bear Dog”
Scientific classification
Kingdom: Animalia
Phylum: Chordata
Class: Mammalia
Order: Carnivora
Suborder: Caniformia
Family: Amphicyonidae
Subfamily: Amphicyoninae
Genus: Agnotherium
Wolf
Kingdom: Animalia
Phylum: Chordata
Class: Mammalia
Order: Carnivora
Suborder: Caniformia
Family: Canidae
Genus: Canis
Species: C. lupus
Fox
Kingdom: Animalia
Phylum: Chordata
Class: Mammalia
Order: Carnivora
Family: Canidae
Genus: Vulpes
Species: Vulpes vulpes
German Shepherd, Doberman, Chihuahua, insert any domestic dog here
Kingdom: Animalia
Phylum: Chordata
Class :Mammalia
Order: Carnivora
Family: Canidae
Genus: Canis
Species: Lupis Familiaris
Why would you want 500 lbs. dog ?? It not going to live very long
http://mentalfloss.com/article/49358/why-don’t-big-dogs-live-long-small-dogs
LoL, i know you’re joking.
I think it’s the 600 pound “dogs” doing the shopping at walmart to feed themselves.
While technically you are correct, and maybe i wasnt clear cause i got interrupted i dont know how many times trying to write the post, P. l. atrox went bye bye when the Megafauna Shopping mart closed, along with his cave cousins in europe etc.
That left the african and asiatics, who got limited to “Which was ALL of africa, some of southern europe, some of southern asia, and east central india” when the great grocery store closed.
I dont know how social, if at all, the other lines of Lions were.
History needed to include the “Fossil Record” on DVD 
would make things easier
~11k years ago - Right about the time Mankind showed up in North America. Coincidence isn’t causality, but it bears some consideration.
Yea ive heard all the caveman killed the world stuff, i dont buy it though.
Native americans did not extinct the bison, guys with rifles did, and we are talking about a greatly similar type of people 13,000ya
Also I really doubt there was a large enough population of wasteful humans to eradicate all of what was.
Most recent evidence gives a 4000+ year overlap. That’s a long time for a superpreditor to do its work.
Bison are alo a LOT more efficient than the megafauna. They breed faster, and have much more sophisticated herd behaviors (as best as can be deterimined). Comparing the wooly rhino or the mastadon to the bison isn’t really an apples-to-apples comparison.
Really, though, I subscribe to the theories that suggest that humans were just the final straw that tipped already-stressed megafauna populations over into extinction.
I’d say if their was enough interest, probably. The talk about evolution, etc., although interesting doesn’t really apply as the OP asked about breeding a 500 lb dog. As in you take big dogs and breed them with big dogs and keep doing that over and over until you achieve the objective.
An article of note is this one where a geneticist breed a bobtail into boxers in relatively short time. Kind of cool if you think about it.
Below are two links for two very large dogs, like huge. If you were to keep breeding for this, I think you could come up with a Great Dane/Mastiff combo that would hit 500 pounds.
Both those dogs were at the upper limit for their bone and joint structure, not to mention their ligaments and connective tissue. Structurally, they represent the near-upper limit for what the physical structure of a dog will support. There’s a reason bears are plantigrade instead of digitigrade.